Pastuszak-Lewandoska D, Kordiak J, Czarnecka K H, Migdalska-Sęk M, Nawrot E, Domańska-Senderowska D, Kiszałkiewicz J M, Antczak A, Górski P, Brzeziańska-Lasota E
Department of Molecular Bases of Medicine, Medical University of Lodz, Pomorska 251, C-5, 92-213, Lodz, Poland.
Department of Chest Surgery, General and Oncological Surgery University Hospital No. 2, Medical University of Lodz, Lodz, Poland.
Med Oncol. 2016 Aug;33(8):96. doi: 10.1007/s12032-016-0815-z. Epub 2016 Jul 22.
Lung cancer is the most common cause of death in men and second only to breast cancer in women. MicroRNAs (miRNAs) are involved in tumorigenesis and function as oncogenes or tumor suppressor genes. Among other genes, miRNAs regulate matrix metalloproteinases (MMPs), the proteolytic enzymes playing a significant role in the degradation of extracellular matrix, enhancing tumor invasion and metastasis. The aim of the study was to evaluate the expression levels of selected miRNAs: miR-26a, miR-29b and miR-519d, and their target gene, matrix metalloproteinase-2 (MMP-2) in patients with non-small cell lung cancer (NSCLC). The results were correlated with tumor staging, NSCLC histopathological subtypes and patients' demographical features to assess the possible diagnostic/prognostic value of the studied miRNAs and MMP-2. Total RNA was isolated from 38 NSCLC tissue samples, and the expression analysis was performed using TaqMan(®) probes in qPCR assay. The results indicated underexpression of selected miRNAs and overexpression of MMP-2. The decrease in miRNA-29b expression was statistically significant and differentiated NSCLC histopathological subtypes. Additionally, statistically significant negative correlation was found between MMP-2 expression and its regulatory miR-26a. There are very few studies reporting miRNA-MMPs analysis on mRNA level in lung cancer, and no similar reports are available from Polish population. The results of our pilot study indicated the diagnostic potential of miR-29b and MMP-2, an inverse association between miR-26a and MMP-2, and proved the role of MMP-2 and the studied miRNAs in lung carcinogenesis. Further studies are needed to verify their potential usefulness for the treatment of lung cancer.
肺癌是男性最常见的死因,在女性中仅次于乳腺癌。微小RNA(miRNA)参与肿瘤发生,并作为癌基因或肿瘤抑制基因发挥作用。在其他基因中,miRNA调节基质金属蛋白酶(MMP),这些蛋白水解酶在细胞外基质降解中起重要作用,增强肿瘤侵袭和转移。本研究的目的是评估非小细胞肺癌(NSCLC)患者中选定的miRNA:miR-26a、miR-29b和miR-519d及其靶基因基质金属蛋白酶-2(MMP-2)的表达水平。将结果与肿瘤分期、NSCLC组织病理学亚型和患者人口统计学特征相关联,以评估所研究的miRNA和MMP-2的可能诊断/预后价值。从38个NSCLC组织样本中分离总RNA,并使用TaqMan®探针在qPCR分析中进行表达分析。结果表明选定的miRNA表达不足,MMP-2表达过度。miR-29b表达的降低具有统计学意义,并且区分了NSCLC组织病理学亚型。此外,在MMP-2表达与其调节性miR-26a之间发现了具有统计学意义的负相关。很少有研究报道肺癌中miRNA-MMPs在mRNA水平上的分析,波兰人群中也没有类似的报道。我们的初步研究结果表明miR-29b和MMP-2的诊断潜力,miR-26a和MMP-2之间的负相关,并证明了MMP-2和所研究的miRNA在肺癌发生中的作用。需要进一步研究以验证它们在肺癌治疗中的潜在用途。